All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Studies with human and mouse embryonic stem cells (ESCs) have shown that a common precursor to both vascular (endothelial and smooth muscle cells) and hematopoietic cell lineages called the hemangioblast can be produced from ESC-derived embryoid bodies in culture. The inventors' group has developed a simple strategy to efficiently and reproducibly generate hemangioblasts from multiple hESC lines under serum- and stromal-free conditions, which is important for their productive use in regenerative medicine. Previous work his shown that hESC-derived hemangioblasts can effectively differentiate into erythroid and myeloid lineages, but their ability to produce lymphoid lineage cells, including those with immunotherapeutic potential, is relatively unknown.
Natural killer (NK) cells, which arise through the lymphoid lineage and are part of the innate immune system, may be used in anti-cancer therapy as they have been found to detect and kill certain types of tumor cells. Dendritic cells (DCs), which mostly arise through the myeloid lineage (from monocytes) and are part of the adaptive immune system, may be used to enhance antigen-specific immune responses through their ability to present antigen to and stimulate both naïve and memory T cells (e.g., DC-based vaccine therapy).
Given the immunotherapeutic potential, there exists a need in the art for a method of generating natural killer (NK) cells and dendritic cells (DCs).